85% of sporadic hyperparathyroidism cases have a solitary adenoma. The remainder of cases have multiple tumors. About 95% of all cases achieve a long remission at initial operation. Adverse outcomes are increased in multigland disease. The cause of parathyroid adenoma is believed to be mutation of some gene, with overgrowth of a clone. Mutation of the cyclin D1 (PRAD1) accounts for only 3-4%. Sporadic (nonhereditary) mutation of the MEN1 gene is the most common known mutation, causing 25-30% of adenomas. Of the 15% with multigland disease, 5% (1/3 of 15%) have a familial form. Most have MEN1 or familial hypocalciuric hypercalcemia. About 1% have familial isolated hyperparathyroidism (FIH). When 40 nonsyndromal kindreds with FIH were tested for occult syndromal mutations, there were no MEN1 mutations but about 10% had CASR mutation or HRPT2 mutation. The underlying gene(s)for the remaining majority of FIH are not known, but mutation of a gene on chromosome 2 seems likely, from linkage analysis.